Nitrogen heterocycles examples

Reductive cyclization of the 2-halogenophenyl group onto an adjacent phenyl substituent is a useful reaction for the preparation of condensed ring nitrogen heterocycles. Examples of the process include the formation of aromatic and conjugated 7t-systems [168, 169]. It has been applied to the synthesis of an aporphine... 

The metaiation of heterocycles is possible without the aid of a directing group. This type of reaction is most common in the ir-excessive heterocycles, and is most important for thiophenes. For nitrogen heterocycles, examples of unactivated lithiation of ir-excessive azoles have been reported, and are summarized below. ir-Deficient heterocycles such as pyridine are resistant to unactivated lithiation, although pyridine can be metalated with low regioselectivity using butylsodium. Pyridines also form weak complexes with fluoro ketones the complex of 4-r-butylpyridine and hexafluoroacetone can be lithiated and added to benzaldehyde in 60% yield. ... 

Many saturated nitrogen heterocycles are commercially available from industrial processes, which involve, for example, nucleophilic substitution of hydroxyl groum by amino groups under conditions far from laboratory use, e.g. 

These contracted names of heterocyclic nitrogen compounds are retained as alternatives for systematic names, sometimes with indicated hydrogen. In addition, names of 0x0 derivatives of fully saturated nitrogen heterocycles that systematically end in -idinone are often contracted to end in -idone when no ambiguity might result. For example. 

No simple electrophilic substitution, for example nitrosation, nitration, sulfonation or halogenation of a C—H bond, has so far been recorded in the pteridine series. The strong 7T-electron deficiency of this nitrogen heterocycle opposes such electrophilic attack, which would require a high-energy transition state of low stability. 

One interesting problem frequently recurring in heterocyclic chemistry, particularly with respect to nitrogen heterocycles, is tautomeric equilibria. Too many methods are available for the elucidation of equilibrium positions and tautomeric equilibrium constants (Kj) to adequately review the whole question here. However, the Hammett equation provides one independent method this method has the advantage that it can be used to predict the equilibrium position and to estimate the equilibrium constant, even in cases where the equilibrium position is so far to one side or the other that experimental determination of the concentration of the minor component is impossible. The entire method will be illustrated using nicotinic acid as an example but is, of course, completely general. 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

Phosphines behave similarly, and compounds of the type R3P and R4P X can be so prepared. The reaction between triphenylphosphine and quaternary salts of nitrogen heterocycles in an aprotic solvent is probably the best way of dealkylating the heterocycles, for example, ... 

Protonated nitrogen heterocycles can be carbalkoxylated" by treatment with esters of a-keto acids and Fenton s reagent. Pyridine is carbalkoxylated at C-2 and C-4, for example. The attack is by "COOR radicals generated from the esters ... 

A -Acyl salts of nitrogen heterocycles phosphorylate in the hetero-ring, rather than at the carbonyl group, to give, for example, (25). The addition of dialkyl phosphites to ynamines has been reported. The products... 

Many companies spiecialize in the production of chemicals grouped in chemical trees characterized by the same chemical roots (compounds) or the same/similar method of manufacturing. Examples are the Lonza trees based upon (I) hydrogen cyanide, (2) ketene (H2C=C=0) and diketene (4-methyleneoxetan-2-one), and (3) nitrogen heterocycles. A different t3q)e of tree is that of DSM Chemie Linz, which branches out from ozonolysis as the core technology (Stinson, 1996). Wacker Chemie has developed its chemical tree leading to acetoacetates, other acylacetates, and 2-ketones (Stinson, 1997). Table 1.1 shows examples of fine chemicals. 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

The hetero-DA reaction with azadienes, a well known synthetic method for obtaining nitrogen heterocycles, suffers from some difficulties, because of the low reactivity of the diene. For example, azadiene 2 did not react with DMAD under the action of conventional heating [22], Sequential exposure to MW irradiation (30 W) for 10 min on a graphite support (Tmax = 171 °C) led to the adduct 7 with 60% conversion (50% in isolated product) [26, 27]. An equivalent yield was obtained by ultrasonic irradiation of the neat reaction mixture at 50 °C for 50 h [29]. 

The azaallyl anions 85.11-85.17 derived from cyclic nitrogen heterocycles generally react with 6 to afford the corresponding bridgehead nitrogen heterocycles. Some of the examples studied by our group are described below. 

A variety of cyclic olefins (5-, 6-, and 7-membered) that contain nitrogen have been prepared via ring-closing metathesis, for example as shown in Eq. 33 [209]. Other examples are shown in Eqs. 34 [210] and 35 [211]. A variety of pyrrolizi-dines, indolizidines, quinolizidines, pyrrolidinoazocines, piperidinoazocines, and other fused nitrogen heterocycles have also been prepared via ROM (e.g., Eq.36 [212,213]). 

Photolysis or thermolysis of heteroatom-substituted chromium carbene complexes can lead to the formation of ketene-like intermediates (cf. Sections 2.2.3 and 2.2.5). The reaction of these intermediates with tertiary amines can yield ammonium ylides, which can undergo Stevens rearrangement [294,365,366] (see also Entry 6, Table 2.14 and Experimental Procedure 2.2.1). This reaction sequence has been used to prepare pyrrolidones and other nitrogen-containing heterocycles. Examples of such reactions are given in Figure 2.31 and Table 2.21. 

In this section I refer to a number of cycloadditions which cannot be categorized into the above-described types. For example, Murai and colleagues reported the four-component coupling of alkyne, hydrazone, hydrosilane and CO. Here, the [Ir4(CO)i2]-catalyzed reaction proceeded under pressurized CO conditions at high temperature, whereby a seven-membered nitrogen heterocycle was obtained (Scheme 11.37) [48]. 

The relative basicity of an aromatic nitrogen heterocycle is dictated by the ring size, the presence of any other heteroatoms, and possible effects from substituents. It is potentially a rather more complex problem than with, say, simple amines, and should be approached logically and systematically. In practice, these examples do not present particularly difficult problems. 

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